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Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT.

Authors :
Noviello M
Manfredi F
Ruggiero E
Perini T
Oliveira G
Cortesi F
De Simone P
Toffalori C
Gambacorta V
Greco R
Peccatori J
Casucci M
Casorati G
Dellabona P
Onozawa M
Teshima T
Griffioen M
Halkes CJM
Falkenburg JHF
Stölzel F
Altmann H
Bornhäuser M
Waterhouse M
Zeiser R
Finke J
Cieri N
Bondanza A
Vago L
Ciceri F
Bonini C
Source :
Nature communications [Nat Commun] 2019 Mar 25; Vol. 10 (1), pp. 1065. Date of Electronic Publication: 2019 Mar 25.
Publication Year :
2019

Abstract

The major cause of death after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for acute myeloid leukemia (AML) is disease relapse. We investigated the expression of Inhibitory Receptors (IR; PD-1/CTLA-4/TIM-3/LAG-3/2B4/KLRG1/GITR) on T cells infiltrating the bone marrow (BM) of 32 AML patients relapsing (median 251 days) or maintaining complete remission (CR; median 1 year) after HSCT. A higher proportion of early-differentiated Memory Stem (T <subscript>SCM</subscript> ) and Central Memory BM-T cells express multiple IR in relapsing patients than in CR patients. Exhausted BM-T cells at relapse display a restricted TCR repertoire, impaired effector functions and leukemia-reactive specificities. In 57 patients, early detection of severely exhausted (PD-1 <superscript>+</superscript> Eomes <superscript>+</superscript> T-bet <superscript>-</superscript> ) BM-T <subscript>SCM</subscript> predicts relapse. Accordingly, leukemia-specific T cells in patients prone to relapse display exhaustion markers, absent in patients maintaining long-term CR. These results highlight a wide, though reversible, immunological dysfunction in the BM of AML patients relapsing after HSCT and suggest new therapeutic opportunities for the disease.

Details

Language :
English
ISSN :
2041-1723
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
30911002
Full Text :
https://doi.org/10.1038/s41467-019-08871-1